Prostate cancer (CaP) is the most commonly diagnosed cancer in American men with an estimated 189,000 new cases in the year 2002 and the second most common cause of death from cancer in American men. (Jamel et al., Cancer J for Clinicians, 52: 23-47, 2002.) Prostate cancer, like other cancers, can be viewed as a breakdown in the communication between tumor cells and their environment, including their normal neighboring cells. Growth-stimulatory and growth-inhibitory signals are routinely exchanged between cells within a tissue. Normally, cells do not divide in the absence of stimulatory signals, and, likewise, will cease dividing in the presence of inhibitory signals. In a cancerous or neoplastic state, a cell acquires the ability to “override” these signals and to proliferate under conditions in which a normal cell would not grow.
In general, tumor cells must acquire a number of distinct aberrant traits in order to proliferate in an abnormal manner. In addition to abnormal cell proliferation, cells must acquire several other traits for tumor progression to occur. For example, early on in tumor progression, cells must evade the host immune system. Further, as tumor mass increases, the tumor must acquire vasculature to supply nourishment and remove metabolic waste. Additionally, cells must acquire an ability to invade adjacent tissue. In many cases cells ultimately acquire the capacity to metastasize to distant sites.
In the realm of cancer therapy it often happens that a therapeutic agent that is initially effective for a given patient becomes, overtime, ineffective or less effective for that patient. The very same therapeutic agent may continue to be effective over a long period of time for a different patient. Further, a therapeutic agent, which is effective, at least initially for some patients, is completely ineffective or even harmful for other patients.
Chemotherapy, androgen withdrawal, surgery and radiation therapy are some of the current forms of prostate cancer treatment. Androgen withdrawal, by castration or through the use of an anti-androgenic drug, is the preferred treatment method for prostate cancer. One drug used to initiate androgen withdrawal is Bicalutamide. Bicalutamide (casodex) is a relatively potent, orally active anti-androgenic drug. Approximately 80% of the prostate cancer patients treated with bicalutamide respond to the treatment; however, most patients eventually relapse. Indeed, no current treatment is completely effective. The majority of the CaP related deaths, estimated to be 30,200 in the year 2002, is likely a result of failure of all currently available conventional treatments.
Because of the problems associated with conventional therapy, or sometimes also the cost, CaP patients often seek unproven therapeutic approaches (Jacobson and Chetty (2001) Curr Oncol Rep 3:448-52.) In fact, poor efficacy of conventional chemotherapeutic drugs against metastatic hormone-refractory prostate cancer (CaP) drives patients to try “alternate medicine.” It is estimate that 30%-40% of men with CaP experiment with one or more complementary therapies which include high dose vitamins and minerals, herbal preparations, plants and plant extracts, and supplements of soy, saw palmetto etc. (Jones et al., (2002) Urology 59:272-276.)
In view of the above considerations, it is clear that there is a need to supplement existing methods of inhibiting prostate cancer cell invasiveness and metastasis. Current approaches rely on highly cytotoxic compounds that cause ancillary debilitating sickness in patients, or use methodology that is expensive, procedurally difficult, and unpredictable. Accordingly, it would be useful to identify an anti-prostate cancer composition that is efficacious and well tolerated in humans.